Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

Baseline dependent minimally important differences for clinical outcomes of pulmonary rehabilitation in people with COPD.

INTRODUCTION: Minimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics. METHODS: A database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI. RESULTS: MID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m2). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined. DISCUSSION: Findings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined.

Test-retest reliability, construct validity and determinants of 6-minute walk test performance in adult patients with asthma.

INTRODUCTION AND OBJECTIVES: Current knowledge regarding the measurement properties of the 6-minute walk test (6MWT) in patients with asthma is limited. Therefore, the aim of this study was to assess the test-retest reliability, measurement error and construct validity of the 6MWT and identify determinants of 6-minute walk distance (6MWD) in patients with asthma. PATIENTS AND METHODS: 201 asthma patients referred for pre-pulmonary rehabilitation assessment, were retrospectively analyzed (age 61±12 years, 42% male, FEV1 78±27% predicted). Patients performed two 6MWTs on subsequent days using a 30 m straight walking course. Other measurements included resting dyspnea, maximal exercise capacity, body composition, pulmonary function, pulmonary and quadriceps muscle strength and symptoms of anxiety and depression. Measurement error (absolute reliability) was tested using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC95%) and Bland and Altman 95% limits of agreement, whereas test-retest reliability (relative reliability) and construct validity were assessed using the intra-class correlation coefficient (ICC2,1) and correlations, respectively. RESULTS: The 6MWD showed excellent test-retest reliability (ICC2,1: 0.91). The mean change in 6MWD after the second 6MWT was 18m (95%CI 11-24m), with 73% of the patients walking further in the second test. The SEM and MDC95% for the 6MWT were 35 m and 98 m, respectively. The best 6MWD correlated strongly with peak oxygen uptake during CPET and resting dyspnea (r = 0.61-0.64) and had no-to-moderate correlations with body composition, pulmonary function, respiratory and quadriceps muscle strength and symptoms of anxiety and depression (r = 0.02-0.45). Multiple linear regression was able to identify maximal workload, BMI, rollator use, maximal expiratory pressure, FEV1 and DLCO as independent determinants of the best 6MWD (R2 = 0.58). CONCLUSIONS: The 6MWT was considered to be reliable and valid in patients with asthma, which strengthens its clinical utility. However, the majority of patients demonstrated a considerable learning effect in the second 6MWT, providing a strong rationale for performing two 6MWTs.

The correlation between quadriceps muscle strength and endurance and exercise performance in patients with COPD.

To determine the association between quadriceps muscle strength (QMS) and endurance (QME) and exercise capacity in patients with COPD after stratification for sex and resting lung function (LF). Data were collected from 3,246 patients with COPD (60% men, 64 ± 9 yr), including measures of exercise capacity [peak aerobic capacity (peakV̇o2), 6-min walk distance (6MWD)] and isokinetic QMS and QME. Patients were stratified for sex, forced expiratory volume in 1 s (>50/≤50% predicted), single breath carbon monoxide diffusing capacity (>50/≤50% predicted), and residual volume (>140/≤140% predicted). After stratification for resting LF, QMS and QME were significantly associated with peakV̇o2 (r range: 0.47-0.61 and 0.49-0.65 for men and 0.53-0.66 and 0.48-0.67 for women, respectively) and 6MWD (r range: 0.29-0.42 and 0.44-0.55 for men and 0.25-0.54 and 0.34-0.55 for women, respectively) (P < 0.001). Regression models demonstrated that QMS and QME were significant determinants of peakV̇o2 (explained variance R2 range: 35.6%-48.8% for men and 36.8%-49.0% for women) and 6MWD (R2 range: 24.3%-43.3% for men and 28.4%-40.3% for women), independent of age and fat-free mass. Quadriceps muscle function was significantly associated with peakV̇o2 and 6MWD in male and female patients with COPD after stratification for resting LF, in which QME appear to be a more important determinant than QMS. This underlines the importance of systematically evaluating both quadriceps muscle strength and endurance in in all patients with COPD.NEW & NOTEWORTHY Our findings identified quadriceps muscle function as an important determinant of exercise capacity across a wide spectrum of lung function. Quadriceps muscle endurance appears to be a more important determinant than quadriceps muscle strength, underlining the importance of including both the measurement of quadriceps muscle strength and endurance in routine assessment for all patient with COPD.

Impact of pulmonary rehabilitation on activities of daily living in patients with chronic obstructive pulmonary disease.

A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). We aimed to determine the effects of a comprehensive 8-wk pulmonary rehabilitation program on the physiologic response to and performance of ADLs in patients with COPD. Before and after pulmonary rehabilitation, 31 patients with COPD [71% men; mean age: 64.2 (SD 8.4) years; mean forced expiratory volume in the first second: 54.6 (SD 19.9) % predicted] performed physical function tests, the Canadian Occupational Performance Measure (COPM), and an ADL test consisting of the following: putting on socks, shoes, and vest; stair climbing; washing up four dishes, cups, and saucers; doing groceries and putting away groceries in a cupboard; folding eight towels; and vacuum cleaning for 4 min. Metabolic load, ventilation, and dynamic hyperinflation were assessed using an Oxycon mobile device. In addition, symptoms of dyspnea and fatigue and time to complete ADLs were recorded. After rehabilitation, patients with COPD used a significantly lower proportion of their peak aerobic capacity and ventilation to perform ADLs, accompanied by lower Borg scores for dyspnea and fatigue. Furthermore, patients needed significantly less time to complete ADLs. Dynamic hyperinflation occurred during the performance of ADLs, which did not change following pulmonary rehabilitation. Changes in physical function, including six-min walk distance, constant work rate test, quadriceps muscle strength, and COPM were significantly correlated with change in average total oxygen uptake during the performance of the ADL test. A comprehensive pulmonary rehabilitation program can improve the physiologic response to and actual performance of ADLs in patients with COPD. NEW & NOTEWORTHY A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). This study clearly demonstrated that a comprehensive pulmonary rehabilitation program can improve the performance of ADLs in patients with COPD, indicated by a significantly shorter time to perform ADLs and a lower metabolic load and dyspnea sensation.

High intensity training in obesity: a Meta-analysis.

INTRODUCTION: High Intensity training (HIT) is a time-effective alternative to traditional exercise programs in adults with obesity, but the superiority in terms of improving cardiopulmonary fitness and weight loss has not been demonstrated. OBJECTIVE: to determine the effectiveness of HIT on cardiopulmonary fitness and body composition in adults with obesity compared to traditional (high volume continuous) exercise. METHODS: A systematic search of the main health science databases was conducted for randomized controlled trials comparing HIT with traditional forms of exercise in people with obesity. Eighteen studies were included in the meta-analysis. The (unstandardized) mean difference of each outcome parameters was calculated and pooled with the random effects model. RESULTS: HIT resulted in greater improvement of cardiopulmonary fitness (VO2max) (MD 1.83, 95% CI 0.70, 2.96, p<0.005; I2=31%) and a greater reduction of %body fat (MD -1.69, 95% CI -3.10, -0.27, p=0.02, I2=30%) compared to traditional exercise. Overall effect for BMI was not different between HIT and traditional exercise. CONCLUSION: Training at high intensity is superior to improve cardiopulmonary fitness and to reduce %body fat in adults with obesity compared to traditional exercise. Future studies are needed to design specific HIT programs for the obese with regard to optimal effect and long-term adherence.

Raw BIA variables are predictors of muscle strength in patients with chronic obstructive pulmonary disease.

BACKGROUND/OBJECTIVES: Although loss of fat-free mass (FFM) and reduced muscle strength are highly prevalent in chronic obstructive pulmonary disease (COPD), only few data are available on the relationships of handgrip strength (HGS) and respiratory muscle strength with body composition in such disease. In particular, we aimed to assess whether raw bioelectrical impedance (BIA) variables were independent predictors of muscle strength in COPD patients, possibly more significant than anthropometric variables and BIA-based estimates of FFM. SUBJECTS/METHODS: Two hundred and thirty-seven COPD patients (161 males and 76 females) underwent respiratory, anthropometric, BIA, HGS and respiratory muscle strength (maximum inspiratory or expiratory pressure=MIP and MEP) measurements. Bioimpedance index (BI index=height square/whole-body impedance) and phase angle (PhA) were considered as raw BIA variables. FFM was estimated using three disease-specific BIA equations. RESULTS: In COPD patients a stronger correlation was observed between HGS and PhA compared to the ones with anthropometric variables or FFM estimates. Multiple regression analysis showed that combining BI index and PhA (plus age in male patients) accounted for 50.2% and 42.6% of the variance in HGS in male and female patients, respectively. Similarly, BI index and PhA emerged as predictors of both MIP and MEP in males, while in females MIP was related only to PhA and MEP only to BI index. CONCLUSIONS: Raw BIA variables are independent and valuable predictors of HGS and respiratory muscle strength in COPD patients. BI index and PhA could provide useful information for evaluating body composition and better assessing muscle strength and physical fitness in COPD.

Use of systemic glucocorticoids and the risk of major osteoporotic fractures in patients with sarcoidosis.

This study revealed the risk of major osteoporotic fracture in patients with sarcoidosis exposed to glucocorticoids. Current use of glucocorticoids was associated with a risk of fracture, with no difference between patients with and without sarcoidosis. Sarcoidosis per se was not associated with an increased fracture risk. INTRODUCTION: Sarcoidosis is a multi-organ, chronic inflammatory, granulomatous disorder that most frequently affects the lungs, lymph nodes, skin, eyes, and liver, but may occur in any organ, including the bones. While oral glucocorticoids (GCs) are commonly used as initial treatment, little is known about the risk of major osteoporotic fractures in patients with sarcoidosis exposed to GCs. METHODS: A case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1995 and December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) of major osteoporotic fractures in subjects with and without sarcoidosis stratified by average daily and cumulative dose exposures. RESULTS: A total of 376,858 subjects with a major osteoporotic fracture and the same number of subjects without this event were identified (mean age 64.2 ± 19.5 years, 69% female). In patients with sarcoidosis (n = 124), current use of GC was associated with an increased risk of major osteoporotic fracture (adjusted (adj.) OR 1.74; 95% CI 1.17-2.58), which dropped to baseline levels after discontinuation. In subjects without sarcoidosis, this risk was comparable (adj. OR 1.36; 95% CI 1.32-1.40). In sarcoidosis patients, cumulative dose 1.0-4.9 g and >10 g prednisolone equivalents were associated with increased risk of major osteoporotic fracture (adj. OR 2.75; 95% CI 1.06-7.14 and 2.22; 95% CI 1.17-4.22, respectively), whereas a cumulative dose of <1.0 g and 5.0-9.9 g was not associated with major osteoporotic fracture risk. CONCLUSION: Both in subjects with and without sarcoidosis, current expose to GC is associated with increased risk of major osteoporotic fractures, with no between-group difference. Sarcoidosis per se was not associated with increased fracture risk. Having sarcoidosis per se, i.e., if not treated with GC, is not a risk factor for fracture, and such patients may only need risk assessment when they commence GC therapy.

How to determine an impaired health status in COPD: Results from a population-based study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a significantly impaired health status and lost work productivity across all degrees of airflow limitation. The current study investigated whether an impaired health status is better represented by the recommended COPD Assessment Test (CAT) cut-point of 10 points, or the 95th percentile of the CAT score in a non-COPD population. Additionally, the impact of COPD on health status in a Dutch population, after stratification for work status, was measured. METHODS: Demographics, clinical characteristics, post-bronchodilator spirometry, and CAT were assessed in subjects from the Longitudinal Aging Study Amsterdam (LASA), a large Dutch population-based study. Normative values for the CAT score were described by percentiles using the mean, standard deviation, median and range. RESULTS: In total, 810 COPD and non-COPD subjects (50.4% male, mean age 60.5 ±; 2.9 years) were analysed. Significant differences were observed in CAT scores between non-COPD and COPD subjects (6.7 ±; 5.2 vs. 9.5 ±; 5.9, p < 0.001 respectively). The proportion of COPD subjects with an impaired health status differed between applying the CAT ≥ 10 cut-point (50.0%) and applying the 95th percentile of CAT in non-COPD subjects (> 18 cut-point; 7.6%). Higher CAT scores were seen in working COPD patients compared with working non-COPD subjects (9.3 ±; 5.2 vs. 6.0 ±; 4.6, p < 0.001). CONCLUSION: We suggest a CAT cut-point of > 18 points to indicate an impaired health status in COPD. This would imply an adaptation of the current GOLD classification of the disease.

Impact of airflow limitation in chronic heart failure.

BACKGROUND: Comorbidities are common in chronic heart failure (HF) patients, but diagnoses are often not based on objective testing. Chronic obstructive pulmonary disease (COPD) is an important comorbidity and often neglected because of shared symptoms and risk factors. Precise prevalence and consequences are not well known. Therefore, we investigated prevalence, pulmonary treatment, symptoms and quality of life (QOL) of COPD in patients with chronic HF. METHODS: 205 patients with stable HF for at least 1 month, aged above 50 years, were included from our outpatient cardiology clinic, irrespective of left ventricular ejection fraction. Patients performed post-bronchodilator spirometry, a six-minute walk test (6-MWT) and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). COPD was diagnosed according to GOLD criteria. Restrictive lung function was defined as FEV1/FVC ≥0.70 and FVC <80% of predicted value. The BODE and ADO index, risk scores in COPD patients, were calculated. RESULTS: Almost 40% fulfilled the criteria of COPD and 7% had restrictive lung disease, the latter being excluded from further analysis. Noteworthy, 63% of the COPD patients were undiagnosed and 8% of those without COPD used inhalation therapy. Patients with COPD had more shortness of breath despite little difference in HF severity and similar other comorbidities. KCCQ was significantly worse in COPD patients. The ADO and BODE indices were significantly different. CONCLUSION: COPD is very common in unselected HF patients. It was often not diagnosed and many patients received treatment without being diagnosed with COPD. Presence of COPD worsens symptoms and negatively effects cardiac specific QOL.

Personalized medicine and chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: The current review summarizes ongoing developments in personalized medicine and precision medicine in chronic obstructive pulmonary disease (COPD). Our current approach is far away of personalized management algorithms as current recommendations for COPD are largely based on a reductionist disease description, operationally defined by results of spirometry. RECENT FINDINGS: Besides precision medicine developments, a personalized medicine approach in COPD is described based on a holistic approach of the patient and considering illness as the consequence of dynamic interactions within and between multiple interacting and self-adjusting systems. Pulmonary rehabilitation is described as a model of personalized medicine. Largely based on current understanding of inflammatory processes in COPD, targeted interventions in COPD are reviewed. Augmentation therapy for α-1-antitrypsine deficiency is described as model of precision medicine in COPD based in profound understanding of the related genetic endotype. SUMMARY: Future developments of precision medicine in COPD require identification of relevant endotypes combined with proper identification of phenotypes involved in the complex and heterogeneous manifestations of COPD.

Bacterial aetiology and mortality in COPD patients with CAP: results from the German Competence Network, CAPNETZ.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality, and chronic obstructive pulmonary disease (COPD) is a frequent comorbidity. The bacterial aetiology of CAP-COPD and its possible associations with serum markers and mortality are incompletely understood. OBJECTIVES: 1) To assess the bacterial aetiology of CAP only and CAP-COPD, and 2) to study the association between bacterial aetiology, empirical antibiotic treatment, serum markers and mortality. METHODS: Of 1288 patients with CAP (57.0% males, age 59.0 years ± 18.5), 262 (20.3%) fulfilled the diagnostic criteria for COPD. Differences between subgroups were investigated using univariate analyses and corrected for multiple comparisons. RESULTS: Streptococcus pneumoniae was the most common pathogen (30.8% CAP only vs. 26.0% CAP-COPD, not significant). Haemophilus influenzae was significantly more frequent in CAP-COPD (5.6% CAP only vs. 26.0% CAP-COPD, P < 0.001). The number given adequate empirical antibiotic treatment was comparable (83.3% CAP only vs. 83.6% CAP-COPD, P > 0.05). The CAP-COPD group had worse CURB-65 and partial pressure of arterial oxygen levels than the CAP only group (P < 0.001). Partial pressure of arterial carbon dioxide levels were increased in CAP-COPD patients without pathogen detection (P < 0.001). Short- (P = 0.011) and long-term mortality (P = 0.006) were highest in CAP-COPD without pathogen detection. CONCLUSION: It is important to identify COPD patients with CAP. In particular, those without bacterial pathogen detection have more severe CAP and are at higher risk of dying. Better understanding of the aetiology could contribute to improved management and treatment of CAP in COPD patients.

[Two sisters with lung emphysema]. / Twee zussen met longemfyseem.

BACKGROUND: α1-antitrypsin is an antiprotease that is mainly produced in the liver; it plays a crucial role in the protection of lung parenchyma against the destructive effects of proteases. Mutations in the α1-antitrypsin gene can cause α1-antitrypsin deficiency. Individuals homozygous for the Z-genotype have drastically lowered serum α1-antitrypsine concentrations and often develop lung emphysema at an early age. CASE DESCRIPTION: A 38-year-old woman and her 43-year-old sister both developed lung emphysema at an early age; this could be attributed to severe α1-antitrypsin deficiency. The only treatment for this condition is α1-antitrypsin supplement therapy, but this therapy is not reimbursed by health insurance companies in the Netherlands. CONCLUSION: α1-antitrypsin deficiency is a relatively rare cause of lung emphysema and can be seen as an orphan phenotype of chronic obstructive pulmonary disease (COPD). We appeal for reconsideration of coverage of α1-antitrypsine supplement therapy by basic health insurance in the Netherlands, on the basis of a recent randomised placebo-controlled study in which the protective effect of this therapy on progressive emphysema was demonstrated by CT lung densitometry.

Relationship between pulmonary rehabilitation and care dependency in COPD.

The aims of this study were to explore care dependency before and after pulmonary rehabilitation (PR) in patients with COPD (n=331) and to compare the response to PR between care dependent and independent patients. At baseline, 85 (25.7%) patients had a Care Dependency Scale (CDS) score ≤68 points and were considered as care dependent. CDS scores of these patients improved after PR (p<0.001). After PR, CDS score of 38 (44.7%) patients with a baseline CDS score ≤68 points increased to >68 points. Patients with a baseline CDS score ≤68 points or >68 points showed after PR a comparable improvement in COPD Assessment Test, Hospital Anxiety and Depression Scale and 6-min walk distance (all p<0.05). TRIAL REGISTRATION NUMBER: NTR3416 (The Netherlands).

Prevalence of thoracic pain in patients with chronic obstructive pulmonary disease and relationship with patient characteristics: a cross-sectional observational study.

BACKGROUND: Objectives of this study were to evaluate the prevalence of thoracic pain in patients with chronic obstructive pulmonary disease (COPD) and its relationship with Forced Expiratory Volume in the first second (FEV1), static hyperinflation, dyspnoea, functional exercise capacity, disease-specific health status, anxiety, and depression. METHODS: This cross-sectional observational study included patients with COPD entering pulmonary rehabilitation. Participants underwent spirometry, plethysmography, and measurement of single breath diffusion capacity. Pain was assessed using a multidimensional, structured pain interview. In addition, dyspnoea severity (Modified Medical Research Council Dyspnoea Scale (mMRC)), functional exercise capacity (six-minute walking distance (6MWD)), disease-specific health status (COPD Assessment Test (CAT)), and symptoms of anxiety and depression (Hospital Anxiety Depression Scale (HADS)) were recorded. RESULTS: 55 of the included 67 participants reported chronic pain (82.1%). 53.7% had thoracic pain. After considering multiple comparisons, only younger age and worse CAT scores were related with the presence of thoracic pain (p = 0.01). There were no relationships between thoracic pain and FEV1, static lung hyperinflation, diffusion capacity, mMRC score, 6MWD, anxiety or depression. CONCLUSION: Thoracic pain is highly prevalent in COPD patients and is related to impaired disease-specific health status, but there is no relationship with FEV1, static hyperinflation, dyspnoea severity or functional exercise capacity.

A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.

Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences.

Comparison of three different techniques for the isolation of viral RNA in sputum.

BACKGROUND: Respiratory infections are a major cause of morbidity and mortality worldwide. A high percentage of all respiratory tract infections are caused by RNA viruses. Real-time PCR is a highly sensitive method for the detection of respiratory viruses in clinical samples. A good RNA isolation protocol is of high importance, since RNA is more unstable than DNA and many clinical samples contain RNAses. OBJECTIVES: To evaluate the performance of three different RNA extraction protocols for the extraction of respiratory viral RNA from sputum samples obtained from patients with the suspicion of a viral respiratory tract infection. STUDY DESIGN: A total of 50 sputum samples, PCR positive for a respiratory RNA virus, were used for viral RNA isolation with the phenol/chloroform method, RTP(®) DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction system. After isolation, real-time PCR was performed for the detection of viral RNA in the sputum samples. RESULTS: The MPLC extraction increased the detection probability from 82% (phenol/chloroform) and 86% (RTP(®) DNA/RNA virus mini kit) to 94%. In 16% the RTP(®) DNA/RNA virus mini kit resulted in lower Ct values compared to the phenol/chloroform method, while in 32% the phenol/chloroform resulted in lower Ct values. CONCLUSIONS: The extraction of viral RNA performed with the MPLC extraction method was superior to the extraction with the RTP(®) DNA/RNA virus mini kit and to the extraction with phenol/chloroform. In general, there was no difference in the detection of viral RNA between the phenol/chloroform extraction method and the RTP(®) DNA/RNA virus mini kit.

Quality of dietary intake in relation to body composition in patients with chronic obstructive pulmonary disease eligible for pulmonary rehabilitation.

BACKGROUND/OBJECTIVES: A poor dietary quality may accelerate disturbances in body composition in chronic obstructive pulmonary disease (COPD), but only limited studies have investigated dietary intake from this perspective. The objective of the current study was to investigate dietary intake in relation to low fat-free mass and abdominal obesity in COPD. SUBJECTS/METHODS: Dietary intake was assessed by means of a cross-check dietary history method in 564 COPD patients referred for pulmonary rehabilitation. The Dutch Food Composition Database was used to calculate nutrient intake, which was compared with the 2006 recommendations from the Dutch Health Council. Body composition was assessed by DEXA scan. RESULTS: In general, the reported intake of macronutrients represented a typical western diet. With regard to micronutrients, vitamin D and calcium intakes were below the recommended levels in the majority of patients (>75%), whereas vitamin A, C and E intakes were below the recommended levels in over one-third of patients. Patients with inadequate vitamin D intake more frequently reported a low intake of protein (P=0.02) and micronutrients (P<0.001). Patients with a low fat-free mass index (FFMI) more often had low intake of protein, while abdominally obese patients more often had low intake of protein and most micronutrients (P<0.05). Patients with both low FFMI and abdominal obesity appeared most often to be consuming a poor-quality diet. CONCLUSIONS: Our data indicate that dietary quality is low in COPD patients referred for pulmonary rehabilitation and differs between patients with different body composition profiles.

Infections with mimivirus in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Antibodies against mimivirus, a recently discovered giant virus, have been found in patients presenting with pneumonia suggesting a potential role for this virus as a respiratory pathogen. Several bacterial and viral pathogens have been associated with the occurrence of acute exacerbations in COPD. However, a large part of these exacerbations have an unknown cause. In the present study we evaluated the presence of mimivirus in sputum samples of COPD patients. METHODS: From March 2009 until January 2010 all sputum samples collected during stable conditions and during exacerbations of COPD patients, referred for pulmonary rehabilitation, were included. All sputum samples were analysed by real-time PCR targeting mimivirus. Furthermore, serum samples were analysed for the presence of antibodies against mimivirus. RESULTS: A total of 220 sputum samples from 109 patients were eligible for inclusion. None of the sputum samples showed the presence of mimivirus DNA. Antibodies against mimivirus were detected in 3 serum samples from 3 patients, of which one showed an increase in antibody-titre. CONCLUSIONS: Although mimivirus was suggested as a potential respiratory pathogen, its presence could not be confirmed in the present study-population of patients with COPD.

Obesity and the lung: 5. Obesity and COPD.

Chronic obstructive pulmonary disease (COPD) and obesity are common and disabling chronic health conditions with increasing prevalence worldwide. A relationship between COPD and obesity is increasingly recognised, although the nature of this association remains unknown. This review focuses on the epidemiology of obesity in COPD and the impact of excessive fat mass on lung function, exercise capacity and prognosis. The evidence for altered adipose tissue functions in obesity--including reduced lipid storage capacity, altered expression and secretion of inflammatory factors, adipose tissue hypoxia and macrophage infiltration in adipose tissue--is also reviewed. The interrelationship between these factors and their contribution to the development of insulin resistance in obesity is considered. It is proposed that, in patients with COPD, reduced oxidative capacity and systemic hypoxia may amplify these disturbances, not only in obese patients but also in subjects with hidden loss of fat-free mass. The potential interaction between abnormal adipose tissue function, systemic inflammation and COPD may provide more insight into the pathogenesis and reversibility of systemic pathology in this disease.